Manufacture of hydroxy acids



I According to the present Patented Mar. 9, 1948 UNITED STATE 2,437,410 r MANUFACTURE OF HYDROXYACIDS i; Karl Heinrich Walter Tuerck, Ba steaa'ana' Hans Joachim Lichtenstein, Epsom, England,

assignors to The Distillers Company, Limited, Edinburgh, Scotland, a British company I 7 No Drawing. Original application November 20, 1943, Serial No. 2,411,700, dated November 26,

11,120, now Patent No. 1946. Divided and this application June 11, 1946, Serial'No. 676,094. In Great Britain April 28,1942

This invention is for provements in or relating to the manufacture of hydroxy acids.

' This application is a division of application Serial No. 511,120, filed November 20,1943,- which has issued as Patent No. 2,411,700,'November 26, 1946. v I Hydroxy acids have hitherto been obtained by the hydroxyl-ation of the corresponding unsaturated acid, for example p-hydroxybutyric acid has been prepared by heating crotonic acid with dilute sulphuric acid for a long period of time. The disadvantages 0f such a method'are the low yields obtained (of the order of 6%), the difliculty of separating the hydroxy acid from the unsaturated acid and the losses of material attendant upon the uneconomic process of recovery of the products from dilute aqueous solutions. Other methods which have been proposed, such as, for example, the oxidation of the corresponding aldehydeby the use of silver oxide, areof academic interest only and have no technical application. v

- We have now found a new methodwhereby the c-hydroxy carboxylic acids can be'produced on a commercial scale.

:There is no suggestion in published works that such hydroxy-aldehydes are autoxidizable asare the simple aldehydes such as acetaldehydeand erotonaldehyde. On the contrary, it has been stated (see Wurtz, Comptes Rendues, volume 76,

page 1167) that-aldol when heatediwith'dry air splits off the elements of water and sets to a vitreous mass which is insoluble in water.

The present invention is based upon the discovery that hydroxy-aldehydev can be subjected to oxidation in the presence of oxygen carriers to produce the corresponding acids, which is a somewhat surprising result as it is well known that 5- hydroxy aldehydes tend to split off the elements of water very readily. I

invention, a process for the manufacture of a fi-monohydroxy-carboxylic acidcomprises oxidising a fi-monohydroxy aldehyde in the liquid phase by passing in molecular oxygen or a gas containing it at an oxygen pressure greater than the partial pressure of oxygen in air, at an elevated temperature and in the presence of an oxygen .carrier catalyst whilst maintaining intimate contact between said molecular oxygen and said p-monohydroxyaldehyde.

Preferably the temperature at which the oxidation is effected lies between 40C. and the normal decomposition temperature of the hydroxy-' aldehyde. The oxygen carrier catalysts, of course, must be substances which do not act on the hydroxyl group eitherof the aldehyde starting mate- '1 Claims. (01. 260-530) rial or the acid product under the conditions obtaining during the reaction.=

The hydroxy-aldehydes which'can be oxidised in accordance with the present invention areespecially those-aliphatic hydroxy-aldehydes having less than eight carbon atomsin the molecule, for examplahydracryla'ldehyde and acetaldolor their a-halogen substitution products such as iii-chloroacetaldol and d-chloro-hydracrylaldehyde.

'We have found thatthe oxidation may readily be carried out evenif the 'acetaldol used-contains -(asis frequently thecase withithe commercial product) more; than50%'byweight'of acetaldehyde either as such, or in the form of a compound with acetaldol which readily dissociates at elevated temperature into free acetaldehyde and acetaldol. Wehave in fact found that oxidation of such a material proceeds more rapidly than with pure acetaldol;

In this case'it is advisable 'to' startthe'oxida- 'tion at a relatively low temperature, e. g., about 35 C., at which temperature the oxidation of acetaldehyde is the principal reaction, and, when the major proportion of the acetaldehyde has been 5 oxidised, gradually to raise the temperature to a final temperature of 40" C., the. main bulk of the :acetaldol being oxidised during "the later stages ofthe reaction.

Intimate contact of'theoxygen or oxygen-con- Otaining gas .with liquid. acetaldol is necessary throughout the oxidation and this may, for example, be accomplished byeflicient stirringior by causing the liquid-gas mixture to flow through suitable reactors, in a state of turbulence.

.The oxygen carrier catalysts which have'been .found to be satisfactory in use and toexercise a catalytic efiect -on-,th e; oxidation reaction are vanadium pentoxidc; vanadic acid, compounds of cobalt, copper, uranium and tungsten; manganous acetate, which is a. commonly used oxygen carrier type-of catalystfor similar oxidations utilising molecular oxygen, is by itself, not sosuitable for theoxidation of the fi-hydroxy aldehydes particu larly if thereae any" unsaturated aldehydes in thereactionmixture; r

We have found that'inanganousacetate, in conjunction, or combination, with other catalysts which are able to p'romote'the oxidation, e. g., cobalt acetate, or copper acetate, is, however, a very satisfactory catalyst for the oxidation of acetaldol to 'beta hydroxybutyric acid according to the "Re e ig i- 5. t p ge s dans; b m ntion and recovery which we have described above in connection with the conversion of acetaldol to beta-hydroxybutyric acid, apply to theconversion of alpha-chloroacetaldol to alpha-,chloro betahydroxybutyric acid.

When oxidising the a-OhlOlO substituted B-hydroxy aldehydes it is preferred to use vanadium compounds as catalysts since-they-retain theiractivity even in the presence of free inorganic acids such as might be produced by the elimination of. hydrogen chloride from the chloroaldehyde.

In most cases, the oxidation reaction will com mence at temperatures of about 40 C. but the optimum temperature of the oxidation will, of course, vary with the nature of the aldehyde undergoing reaction. For example, it is advantageous t oxidise the ,a halogenated B-hydroxyaldehydes such as -chlorohydracryl-aldehyde or ,a-chloroacetaldol t temperatures between 40 taining gas under increased pressure to supplythe molecular oxygen required for the oxidation at an oxygen pressure ,greater than the partial pressure of oxygen in air. In the initial stages of oxidation when using acetaldol containing acetaldehyde, the .acetaldehyde, as indicatedabove, is preferentially oxidised and it i during this stage that an excess of oxygen or oxygencontaining gas is best avoided due to the possibility of formation of an explosive mixture of acetaldehyde and oxygen. When, however, there is no longer any free-acetaldehyde present, we havefound that it is advisable to employ a high concentration of oxygen, i. e., to usea-high oxygen pressure and therefore we use either pure oxygen or a gascontaininga higher proportion of oxygen than is present in air.

We have further found that still further improvement inthe yield obtainable can be achieved by using organic solvents which will keep the hydroxy aldehyde or its "para-form dissolved during the oxidation; suitable solvents are the lower fatty acids such as acetic acid, alcoholand ketones such as acetone. Acetic acid is the preferred solvent and may be added as such or formed in situ by the oxidation of-acetaldehyde, e.'g., that present in impure aldol. The-solvents may be distilled off after the oxidation reaction has been completed or, where alcohol has been used as the solvent, the alcohol may bereacted with ,fi-hydroxy acid "formed in the reaction to produce the corresponding'esters. The reaction *mixturemay be'worked up by distillation of the reaction mixture or by a fractional distillation. On the other hand, where the {3- hydroxy acid is a readily crystallizable acid it may be recovered fromthe reaction .mixture'by crystallization; alternatively, the acid'may be directly-esterified in any convenient'manner.

We have found that if the distillation of 5- hydroxybutyric acid, after distillation under reduced pressure of acetic acid and unchanged acetaldol, is carried out in the presence of steam, in particular superheated steam, or an inert gas, e. g., carbon dioxide or nitrogen, which is passed through the reaction mixture whilst it is maintained at or near its boiling point under a reduced pressure such that the boiling point is about i 12.0+ 4,, C. an increased yield of p-hydroxybutyric acid can be obtained. If the distillation carried out in the absence of such diluents, ihi'ghier condensation products are formed in the still and the boiling point rises to such a point that rapid decomposition and resiniiiication of the reaction products occur. If the distillation-is c arr-ied out in the presence of super- ;heated steam, dehydration of the vd-hydroxybutyric acid to its anhydrides or to crotonic acid is greatly reduced.

' 'We prefer to carry out the separation of the components of the reaction mixture in such a way that the unchanged acetaldol is decomposed to crotonaldehyde. This is because it i difiicult to separate acetaldol as such by distillation from its mixture with-fl-hydroxybutyric acid. If acetic acid is present in the reaction mixture this may be separated by distillation at temperatures slightly in excess of C), and under slight vacuum, under which conditions acetaldol is readily converted to crotonaldehyde, which distills oil with the acetic acid. Under these conditions fl-hydroxybutyric acid does not distill over, A similar result can be brought about by steam distillation at normal pressure.

Although it has previously been reported that ,B-hydroxybutyric acid is volatile in steam, we have found that it forms no azeotropie mixture with wateror with acetic acid and it is thus possible, by steam distillation under reduced pressure followed by fractional condensation, to obai a product c nt ini fi-hydr xy uty ic acid in concentrated form.

The oxidation process may becarried on until the hydroxy-aldehydeis substantially completely oxidised. Any excess of unchanged hydroxyaldehyde may be distilled off as such, or it may be removed from the reaction mixture by treatme thereaction mixture under such conditions that the fl-hydroxy-aldehyde will split off the elements of water to yield the unsaturated aldehyde which is then removed from the reaction mixture in any convenient manner, the conditions of treatment being, of course. such as to avoid splitting off theelements of water from the formed hydroxy acid or its esters.

If desired, it is :possible, for example, by distilling or heating with sulphuric acid to convert the ,p-hydroxy'acid into the corresponding unsaturated acid by splitting off the elements of water; for example, the u-chlorohydracrylic acid may be converted in .this manner to w-chloroacrylic acid.

The following examples illustratethe manner. in which the invent-ionmay be carried into efiect:

'acid. After distilling oif the acetic acid from the reaction'mixture, 25grs. of p-hydroxybutyric acid "distilled overat--130" C, atBmm. Hg pressure.

T083 grs. of freshly distilled acetaldol 0.2 er. of cobalt acetate were added and oxygen passed through the reaction mixtureat-74 C. and 1200 mm. Hg pressure for 60 hours, when 73 grs. of acetaldol had been oxidised to acid. Distillation in ,vacuo gave 42 grs. of ,o-hydroxy butyric acid.

- Example 4 7 60 grs. of freshly distilled acetaldol were dissolved in 40 gm. of n-Ebutanol and 0.2 gr. of cobalt acetate were added. Oxygen was passed .mm. Hg pressure. After 24 hrs. 47 grs. ofacetaldol had been oxidised to acid. Distillation in vacuo gave 38 grs. of p-l'iydroxy-butyric acid,

Example 5 ,B-hydroxy propionic acid was obtained as a clear liquid, insoluble in water. B. .P. 8085 C./8 mm.

. EmampZeG i 35 grs; o-f a-chloroacetaldol were dissolvedin 70 I grs. of acetic acid. Oxygen was passed through the reaction mixture in the presence of 0.05 gr.

of vanadic acid as a catalystat 55-60 C. and

1200 mm. Hg pressure; After 24 hours all the achloroacetaldol present initially had been oxidised.

It has been found that although in Exampl s 1, 2, 3 and 4 reference has been made to the use of freshly distilled acetaldohimpure aldol, e. g., containing "some free acetaldehy de, will react at least as well as 'the pure acetaldol itself, and therefore the invention is not to be considered as being limited to the oxidation of the pure flhydroxy aldehyde, as the presence of small amounts of simpler aldehydes has been found not to interfere with the reaction or as already stated, have actually increased the rate of reaction.

Example 7 In a reactor, provided with means for cooling and heating and with-a fast-running efficient stirrer, a mixture of 600 parts of acetic acid and 1200 parts of crude aldol are agitated while oxygen is passed at normal pressure at such a rate that about 10% of the volume of the gas introduced leaves the reactor. The crude aldol which through the reaction mixture at 55 C. and 11 200 is used contains about 50% aldol and 50% acetaldehyde, partly as such and partly combined with aldol. The reaction mixture further contains 2 parts of cobalt acetate, 0.5 part of copper acetate and 0.1 part of manganese acetate. The

oxidation starts --at 35 C.- at wnicntemperature mainly the acetaldehyde present is oxidised to acetic -acid.- After 2 hours the temperature is raisedto 55 Cgandfinall'y at 70'l5 C. The oxidation is carried on for four hours at which point the aldol content has dropped to about 5%.

"I'he 'reaction mixture, which contains about 32% p-hydroxybutyric acid and 60% acetic acid is distilled at normal or slightly reduced pressure whilst the temperature in the still, heated indirectly by means of steam, is gradually raised to 140 C., live steam being admitted after the bulk oi'the acetic acid has distilled off. Finally, the pressure is reduced to 12 mm. and the p-hydroxybutyric acid distilled over with live steam at to -C. at a strength of 90%. By the use of fractional condensation (e. g., by maintaining the first condenser at 50 C.) an acid of more than 96% strength can be obtained. The temperature qin'the still remains constant until all theacid has been distilled. A residue of 21 parts by weight remains in the still, the residue being easily removable since it shrinks (on cooling) to a brittle non-adherent powder easily soluble in acetic acid. V The acetic acid was obtained asan 82% acid, containing crotonaldehyde formed from the unreacted aldol. It is easily freed from crotonaldehydeby fractional distillation, an azeotropie mixture of water and crotonaldehyde being obtained as head product, boiling at 84 C. at normal pressure. Only 1.5% of the fl-hydroxybutyric acid was-found in the acetic acid fraction.

"If the reaction mixture was ldistilledat' 10 mm. without the aid of steam, the temperature rose steadily from 120 to C. and during the later stages of distillation, dehydration of fi-hydroxybutyric acid to crotonic acid occurs. In this case lowing example illustrates the continuous method of operation.

' Example 8 Amixture of acetic acid and crude acetaldol is oxidised in an loxidiser as in Example 7 the said 'oxidiser however being provided with means for continuously feeding in the crude acetaldoiand with means for continuously drawing off part of the reaction liquors.

The oxidation is carried out as described in Example until the acetaldol content of the reaction liquor has dropped to 10% which crude acetaldol, containing 0.1% by weight of copper acetate and 0.1% by weight of cobalt acetate, is continuously fed in at such a rate that the acetaldol content of the reaction liquor in the 'oxidiser is maintained at about 10 by weight.

An amount of the reaction liquors, corresponding to the volume of input of crude acetaldol, is

continuously withdrawn from the oxidiser and unreacted acetaldol is stripped therefrom by means of steam in such a manner that it is converted to crotonaldehyde as hereinbefore described.

In this manner, 100 grams of crude aldol can be oxidised per hour giving a yield of ,B-hydroxybutyric acid amounting to 85% based on the acetaldol treated.

The temperature at which the reaction is carby weight after 7 'ried out is maintained at 70 C thrOughout; if necessarya scrubbing column forrecovering acetaldehyde from the effluent gases may beprovided.

Instead of utilising the oxidiser described, any other arrangement may be used which will give the necessary intimate contact between thereactants. If a packed column is used for the reaction vessel it is preferred to operate with such a rate of flow that the liquid-gas mixture exhibits turbulent flow throughout the contact, or reaction, zone.

What We claim is:

1. A process for the manufacture of alphachloro-beta-hydroxy propionic acid which comprises oxidising alpha-chloro-beta-hydroxy propionaldehyde in solution in an organic solvent substantially inert under the conditions of oxidation and not destructive of the said aldehyde and other reaction products of the process by the action of molecular oxygen, at an oxygen pressure greater than the partial pressure of oxygen in air, at a temperature between 40 and 80 C. and in the presence of vanadic acid as oxidation-catalyst whilst maintaining intimatecontact between said molecular oxygen and said aldehyde to produce a reaction mixture containing alpha-chloro-betahydroxy propionic acid.

2. A process for the manufacture of alphachloro-beta-hydroxy butyric acid which comprises oxidising alpha-chloro-acetaldol in solution in an organic solvent'substanti'ally inert under the conditions of oxidation and not destructive of the said aldehyde and other reaction products of the process by the action of molecular oxygen, at an oxygen pressure greater than'the partial pressure of oxygen in air, at a temperature between 40 and 80 C. and in the presence of vanadic acid as oxidation catalyst whilst maintaining intimate contact between said molecular oxygen and said aldehyde to produce a reaction mixture containing alpha-chloro-beta-hydroxy butyric acid.

3. A process for the manufacture of alphachloro-beta-hydroxy propionic acid which comprises oxidising alpha-chloro-ibeta-hydroxy propionaldehyde in solution in acetic acid by the action of molecular oxygen, at an oxygen pressure greater than the partial pressure of oxygen in air, at a temperature between 40 and 80 C. and in the presence of Vanadic acid as oxidation catalyst whilst maintaining intimate contact between said molecular oxygen and said aldehyde to produce a reaction mixture containing alpha-chloro betahydroxy propionic acid.

4. A process which comprises, oxidising a sub- 8 stance selected from the group consisting of alpha-chloro-acetal'dol and alpha-chloro-betahydroxy propionaldehyde by the action of molecular oxygen at a pressure greater than oneflfth of sin-atmosphere, at a-temperature between and C. and in the presence of an oxygencarrier catalyst, whilst maintaining intimate contact between said molecular oxygen and said substance to produce a reaction mixture containin the acid corresponding to such substance, said oxidation catalyst being selected from the group consisting of the compounds of vanadium, cobalt,

copperand manganese;

5. A process according to claim 4 wherein vanadic acid is'employed as the oxygen-carrier catalyst.

'6. A process according to claim 4 wherein vanadic acid is employedas the oxygen-carrier catalyst and the reaction is carried out in the presence of acetic acid.

7. A process which comprises, oxidising alphachloro-acetaldol dissolved in acetic acid by the action of molecular oxygen at a pressure greater thanone-fifth of an atmosphere, at a temperature between40 and 80 0., and in the presence of vanadic acid, whilst maintaining intimate contact between said molecular oxygen and said alphachloro-acetaldol solution to produce a reaction mixture containing alpha-chloro-beta-hydroxy butyric acid.

KARL HEINRICH WALTER TUERCK. HANS J OACHIM LICI-ITENSTEIN.

REFERENCES CITED The following references areof record in the file of this patent:

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